Take an interception back to the house in a Play Now or Dynasty Mode game.

Achievement Guide for Pick 6!

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To get an interception you'll want to step in front of where you predict the ball will go before the QB throws it.

One pretty much fool-proof strategy for intercepting a ball is to use two controllers, the one that you want the achievement with should be the one on defense obviously. Now on offense with your 2nd controller you'll want to pick a quick developing play like Quick Slants under the Pass option, after doing that slowly tap X or Y and position a player in between the ball being thrown and the defender.

This isn't *guarenteed* to get you a Pick 6, because you still have to get it back to the Endzone for a Touchdown after that, but it'll certainly help along the way.

For those wondering what an interception really looks like executed I included a video from IGN below to hopefully help you out. The first two plays aren't the inception, the last 20 seconds of the video have it.

Cheers, and comment if you need further help/clarification. And up-vote if this solution helped you, hopefully it did! Good luck!